用于治疗弥漫性大 B 细胞淋巴瘤的双重 PI3K/HDAC 抑制剂的生物评价。
Bioevaluation of a dual PI3K/HDAC inhibitor for the treatment of diffuse large B-cell lymphoma.
机构信息
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; CAMS Key Laboratory of Small Molecule Immuno-Oncology Drug Discovery, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; CAMS Key Laboratory of Small Molecule Immuno-Oncology Drug Discovery, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
出版信息
Bioorg Med Chem Lett. 2022 Sep 1;71:128825. doi: 10.1016/j.bmcl.2022.128825. Epub 2022 May 27.
The synergistic anti-tumor effect by simultaneous inhibitions of PI3K and HDAC has been verified to provide the rationality of PI3K/HDAC dual inhibitors for cancer treatment. Notably, the outstanding effect of PI3K/HDAC dual inhibitors against DLBCL has been paid much attention, especially for RR-DLBCL. Our previously reported 4-methylquinazoine scaffold based PI3K/HDAC dual inhibitors could suppress the growth of solid tumors and hematologic malignancies both in vitro and in vivo, validating the potential as new therapeutic agents for cancer. In this research, we further investigated the anti-tumor activity of one of our compounds against DLBCL cell lines and in vivo zebrafish xenograft model as well as the underlying mechanism, hoping to provide a novel therapeutic agent for treating DLBCL.
同时抑制 PI3K 和 HDAC 的协同抗肿瘤作用已被证实为癌症治疗提供了 PI3K/HDAC 双重抑制剂的合理性。值得注意的是，PI3K/HDAC 双重抑制剂对 DLBCL 的显著疗效引起了广泛关注，特别是对于 RR-DLBCL。我们之前报道的基于 4-甲基喹唑啉骨架的 PI3K/HDAC 双重抑制剂能够在体外和体内抑制实体瘤和血液恶性肿瘤的生长，验证了其作为癌症治疗新药物的潜力。在这项研究中，我们进一步研究了我们的一种化合物对 DLBCL 细胞系和体内斑马鱼异种移植模型的抗肿瘤活性及其潜在机制，希望为治疗 DLBCL 提供一种新的治疗药物。
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